Identification of mouse liver aldehyde dehydrogenases that catalyze the oxidation of retinaldehyde to retinoic acid

Biochem Pharmacol. 1991 Aug 22;42(6):1279-85. doi: 10.1016/0006-2952(91)90266-8.


NAD(P)-linked aldehyde dehydrogenases catalyze the oxidation of a wide variety of aldehydes. Thirteen of these enzymes have been identified in mouse tissues; eleven are found in the liver. Some are substrate-nonspecific; others are relatively substrate-specific. The present investigation sought to determine which of these enzymes are operative in catalyzing the oxidation of retinaldehyde to retinoic acid, a metabolite of vitamin A that promotes the differentiation of epithelial and other cells. Spectrophotometric and HPLC assays were used for this purpose. Enzyme-catalyzed oxidation of retinaldehyde (25 microM) was restricted to the cytosol (105,000 g supernatant fraction) and occurred at a rate of 211 nmol/min/g liver; oxidation of acetaldehyde (4 mM) by this fraction proceeds about ten times faster. At least 90% of this activity was NAD dependent. Of the approximately 10% that was apparently NAD independent, two-thirds was inhibited by 1 mM pyridoxal, a known inhibitor of aldehyde oxidase. Of the six cytosolic aldehyde dehydrogenases, only two, viz. AHD-2 and AHD-7, catalyzed the oxidation of retinaldehyde to retinoic acid. An additional NAD-dependent enzyme, viz. xanthine oxidase (dehydrogenase form), also catalyzed the reaction. Catalysis by AHD-2 accounted for more than 90% of the total NAD-dependent activity. Km values were 0.7, 0.6 and 0.9 microM, respectively, for the AHD-2-, AHD-7- and xanthine oxidase (dehydrogenase form)-catalyzed reaction. AHD-4, an aldehyde dehydrogenase found in the cytosol of mouse stomach epithelium and cornea, did not catalyze the reaction.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aldehyde Dehydrogenase / isolation & purification*
  • Aldehyde Dehydrogenase / metabolism
  • Animals
  • Chromatography / methods
  • Chromatography, High Pressure Liquid
  • Cytosol / enzymology
  • Kinetics
  • Liver / enzymology*
  • Mice
  • Mice, Inbred DBA
  • NAD / pharmacology
  • Oxidation-Reduction
  • Retinaldehyde / metabolism*
  • Solubility
  • Spectrophotometry
  • Tretinoin / metabolism*


  • NAD
  • Tretinoin
  • Aldehyde Dehydrogenase
  • Retinaldehyde